Urolithin A (UA) One of 4 Promising Agents 2024 by Brian Kennedy of NSU

Urolithin A (UA), from berries and pomegranates, boosts muscle and heart function by activating SIRT1, a longevity protein. It has a similar lifespan increase to Rapamycin (Brian Kennedy, NSU). One of 4 promising agents that he is working on (Dec 23)

Some Screenshots:


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Interesting that the lower dose of Urolithin A was better for flies.

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Does anyone know if there is any study of a certain substance or medication that was studied in fruit flies and then worked in similar way in humans?. I thought we only bear resemblance with mammals, or is it that fruit flies have similar biology with us?

It depends on the molecular pathway. Some are carried forward in evolution, (like mTOR and the IGF1 pathways, from flies to mice to humans…). But others much less so.

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Is there a more affordable source than Mitopure? It is so expensive. Saw a cheaper option on Amazon, but do not know the purity and reliability…

https://www.amazon.co.uk/Aeternum-UA-Urolithin-Powder-30g/dp/B0BX3QJJD7

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8.15 Euro per gram

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Mitopure has a boatload of patents around the compound… so we’ll see how the competitive landscape develops … there are Chinese companies selling the raw material… but I wonder about the quality, and how long a company could be expected to resell supplements (in the USA) without legal challenges…

Patents

Mitopure® is the culmination of over 15 years of rigorous scientific research and millions of dollars in investment. We have employed the highest scientific standards and gone to great lengths to ensure that Mitopure is safe, effective, and proprietary.

List of Mitopure Patents (in different countries)

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Is there a way to improve gut microbiome production of urolithin A?

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I think there is…

Research shows that the production of UA can vary between individuals because of differences in the microbiome responsible for breaking down ellagitannins. Ellagitannins are a type of polyphenol found in certain foods. When these foods like berries, pomegranates, and nuts are fermented by gut bacteria, they transform into UA. However, not everyone has a microbiome that can produce UA.

In this article, we are going to focus on a study by Singh et al. (2021), which studied the prevalence of UA producers in a healthy population and whether supplementation with UA can overcome the dietary and microbial barriers to its production and subsequent health benefits.

Research:

Bifidobacterium pseudocatenulatum INIA P815: The first bacterium able to produce urolithins A and B from ellagic acid

https://pubs.acs.org/doi/10.1021/acs.jafc.2c08889

Gut Bacteria Involved in Ellagic Acid Metabolism To Yield Human Urolithin Metabotypes Revealed

https://www.sciencedirect.com/science/article/abs/pii/S1756464618301324

In vivo administration of gut bacterial consortia replicates urolithin metabotypes A and B in a non-urolithin-producing rat model

https://pubs.rsc.org/en/content/articlehtml/2023/fo/d2fo03957e

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Related Threads:

Here: More good news on Urolithin-A

Here: How do I know if I have Urolithin A synthesizing bacteria?

Here: Urolithin A Extends Lifespan in Mice

Fantastic article. Interesting connection to akkermansia

“ What was of significance was that high producers of UA had an increased abundance of Akkermansia muciniphila. An increase in this bacterium in the presence of pomegranate ellagitannins was also seen in an earlier study by Henning et al[vii].”

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Another good article:

Aging and Urolithin A: The Role of the Microbiome

Gut microbiome composition affects how well ellagic acid is converted into the health-promoting urolithin A

A 2022 review takes the magnifying glass to how ellagic acid becomes urolithin A and what the microbiome has to do with it.

There are a lot of steps involved in going from ellagic acid to urolithin A, and many enzymes are involved. In other words, there remain uncertainties about the process. But here is what we do know:

  1. Ellagic acid first undergoes a process that removes a chunk of its chemical structure (a lactone ring), forming Uro-M5 in the colon.
  2. Then, hydroxyl groups ( — OH) are chopped off at different positions. This produces something called tetrahydroxy-urolithins. Getting closer.
  3. Another hydroxyl group is removed, leading to the formation of trihydroxy-urolithins. another step closer to urolithin A.
  4. Moving on through our intestines, a dihydroxylation reaction follows, resulting in dihydroxy-urolithins, including — you guessed it — urolithin A.
  5. (This urolithin A can go on to lose another hydroxyl group to become a monohydroxy-urolithin known as urolithin B. This even less researched urolithin also seems to have some health benefits, but we lack good data on this, especially in humans.)
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Interesting, wasn’t aware that fruit flies had mTOR and the IGF1 pathways similar to humans….

I think Matt Kaeberlein did some of the early work on yeast and mTOR / Rapamycin…

The amino acid sensitive TOR pathway from yeast to mammals

https://www.sciencedirect.com/science/article/pii/S0014579306005084

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Since Urolithin A also works on MTOR, won’t it be the same effect as Rapamycin? You may end up impeding MTOR too much if you combine both treatments. That’d be similar to a higher dose of Rapamycin which may not be good?

Just thinking out loud here… Can someone prove me wrong?

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Have been taking Urolithin A for a couple of months now, feel nothing from it. Rapamycin 6mg weekly however, I feel. Urolithin A is probably quite a weak Mtor inhibitor like Resveratrol. I would not be concerned.

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If I had a mitochondrial problem I’d try it. But I’m not paying a lot for chemicals that don’t provide an effect I can feel or see a big impact in my biomarkers (blood or other).

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Maybe Rapamycin is so potent it overshadows the benefits of Urolithin A. Either way, it’s too expensive for me to take regularly, so I won’t be adding it to my stack.

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Codeage Liposomal Urolithin A Supplement–$3/day.
https://a.co/d/6ohXn5x

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Personally rapamycin is the most “energizing” stack for me amongst the 10 or 12 things that I routat now and then.

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